BACKGROUND: Both Alzheimer's disease (AD) and cerebrovascular atherosclerosis (CA) contributed to dementia in an aged population. Whether they share the same mechanism is unknown.AIM: Our goal was to explore the occurrence rates of CA in AD patients.METHOD: Here we examined the degree of CA in different groups of AD patients with contrast angiography. Ninety-three AD patients were recruited to the present study. Contrast computed tomography scanning and contrast angiography were performed for CA analyses.RESULT: We found that the cerebrovascular plaques were common in AD patients, which was partly correlated with the severity of AD (as determined by cognitive decline).CONCLUSION: We concluded that vascular dementia may partly correlate with AD pathology.

Both Alzheimer’s disease (AD) and cerebrovascular atherosclerosis (CA) contributed to
dementia in an aged population.1–3 Whether the two diseases share a common mechanism or
pathological progression is yet unclear. It is proposed that in AD the amyloid beta peptide mutates
and accumulates to form abnormal aggregates that are resistant to internal clearance,4–6 and these aggregates lead to amyloid plaques (senile plaques) that cause neuronal death as
well as other pathological changes inside the brain, with final functional loss. Conversely, for the
CA multiple small infarcts (atheromatous plaque) formed inside microvasculature and interrupted the
microperfusion.7–9 This also leads to cognitive decline and memory loss as the final
result.

Given the two distinct theories explaining the pathogenesis of AD and CA, there are increasing
studies that show some common risk factors for both diseases, such as apolipoprotein E, age,
smoking, inflammation, and body metabolism.2,10–15 In addition, the coronary atherosclerosis cases are increased in patients with AD
compared to those without.16–18 Conceivably, the CA is higher in patients showing
heart attack. Postmortem studies also reported the existence of CA in many AD patients. In the
present study, we tried to employ radiological approach to investigate the occurrence of CA in AD
patients.

The study was approved by the ethics committee of medical research on human subjects at the
General Hospital of Jinan Military Command, and the researchers obtained written consent from all
subjects as well as their family members.

The data were represented as mean ± standard deviation and analyzed with the Statistical
Package for the Social Sciences 16.0 software (SPSS; IBM Corporation, Armonk, NY, USA) for
statistics. The t-test was used to compare intergroup differences, and
P < 0.05 was considered statistically significant.

Results

Detection of cerebrovascular atherosclerosis

We found that atheromatous plaque is prevalent in AD patients: six of 17 (35.3%) in early
AD; 14 of 26 (53.8%) in mild AD; 20 of 39 (51.3%) in moderate AD; and nine of eleven
(81.8%) in severe AD. In addition, among these cases, both noncalcified and calcified
atheromatous plaques were detected at different possibilities (Figure 1). The percentage of noncalcified mixed and calcified atheromatous
plaques were 44%, 12%, and 44% in early AD; 47%, 21%, and
32% in mild AD; 39%, 15%, and 46% in moderate AD; and 22%,
35%, and 43% in severe AD (Figure
2).

Distribution of atheromatous plaques

We found that noncalcified atheromatous plaques were mainly distributed in the intracranial
arteries (79.2%), mixed plaques in the intracranial arteries (19.1%), and
intracranial internal carotid artery (ICA) (44.3%), calcified plaques in the intracranial
ICA (55.2%), and extracranial arteries (24.7%) across the different AD groups.
Interestingly, we found no obvious differences in plaque distribution across different staged AD
patients (P > 0.05).

Results of atheromatous plaques as vessel occlusion

The differentially composed atheromatous plaques have been shown to be associated with different
levels of vessel occlusion previously. The percentage of severe stenosis (>60%) and
occlusion in the different AD groups were 3.1% (early), 6.7% (mild), 11.3%
(moderate), and 10.7% (severe). The values were significantly different from the severe AD
group to the early/mild AD groups.

Discussion

Few studies have examined the formation of CA plaques in AD patients, specifically.1,2,7,12 It
has been shown that in an aged group with cognitive decline, atherosclerosis plaques could be used
as the marker for vascular dementia.4,7,19 In
the present study, we found that cerebrovascular plaques leading to stenosis or occlusion existed in
AD patients as well. Therefore, the mixed AD/CA pathology should be considered and referred in
clinical diagnosis of certain aged patients with cognitive decline.

The mechanisms underlying such interactions are yet unclear. The common risk factors, such as
apolipoprotein E, age, smoking, inflammation, and body metabolism, do not fully explain the
increased atheromatous plaque occurrence in severe AD, rather than in early AD patients.2,4,5,20–23 We believe it is possible
that the neuronal death and neuroinflammation in late-stage AD triggered the atheromatous plaque
formation. If so, the neuroinflammation would act as the share mechanism in pathogenesis and
progression in patients with severe dementia, providing the common drug target for both
syndromes.

There are certain limitations of the present study. Currently, it is possible to perform magnetic
resonance imaging and positron emission tomography for the tracing of plaque formation in the
vessels, as well as of the amyloid plaques for AD patients.24–26 It will be important to
perform different tests on patients to correlate the changes of CA pathology with AD pathology
(senile/amyloid plaque) progression. Additionally, we did not correlate other syndromes of vascular
dementia into the clinical data of AD patients, taken together with the analysis of stenosis changes
of the vessels.12,27 We expect to perform such studies in the future. Finally, it will be
important to perform these examinations on aged-matched non-AD controls to see if AD pathology
causes increased atheromatous plaque formation.

In conclusion, we believe that the vascular pathology may represent one common phenomenon in AD
patients. The separation of AD and CA pathology might require reconsideration.

Notes

Disclosure

The authors report no conflicts of interest in this work.

The authors received funding from the Guangzhou Baiyun Kexunju Grant 2011-KZ-92.